Cardiac Amyloidosis

What is cardiac amyloidosis?

Cardiac amyloidosis is a condition in which abnormal proteins called amyloid build up in the heart muscle. Amyloid is made of proteins that have folded into the wrong shape and clumped together into stiff fibers the body cannot easily clear. When these fibers collect between the cells of the heart wall, the muscle becomes thicker and stiffer, so the heart has trouble relaxing and filling with blood. Over time this can lead to heart failure, a term that means the heart cannot pump well enough to meet the body’s needs, as well as problems with the heart’s electrical rhythm.

Amyloidosis is a group of diseases rather than a single one. Amyloid can form in many organs, including the kidneys, nerves, liver, and digestive tract. When the heart is the main organ affected, or one of several affected, doctors use the term cardiac amyloidosis. It is considered a relatively uncommon cause of heart disease, but it is increasingly recognized because imaging tests have improved and because it is now known to be more frequent in older adults than previously thought. The two types that most often involve the heart are light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, which are explained in the causes section below. Cardiac amyloidosis is usually managed by cardiologists (heart specialists) working with hematologists (blood specialists) and other teams; at Acibadem, for example, care is coordinated through the Cardiology Department.

Cardiac amyloidosis symptoms

Cardiac amyloidosis symptoms often develop slowly and can be mistaken for other, more common heart conditions or simply for aging. In the early stages some people notice very little. As amyloid continues to accumulate, symptoms of heart failure and rhythm problems tend to appear. Common symptoms include:

• Shortness of breath, first with activity and later even at rest or when lying flat
• Fatigue and reduced ability to exercise
• Swelling (edema) of the ankles, legs, or abdomen caused by fluid buildup
• Palpitations, meaning an awareness of a fast, slow, or irregular heartbeat
• Dizziness or fainting, sometimes related to low blood pressure when standing
• Chest discomfort in some people
• Nausea, poor appetite, or early fullness when the digestive system is congested or also affected
• Unintended weight loss in some cases

Because amyloid can affect other organs, symptoms outside the heart are common and can be important clues. People with ATTR amyloidosis often report numbness, tingling, or pain in the hands and feet (peripheral neuropathy), carpal tunnel syndrome affecting both wrists, a ruptured biceps tendon, or spinal stenosis in the lower back. Some develop a large or unusually firm tongue, easy bruising around the eyes, or diarrhea alternating with constipation, which are more typical of AL amyloidosis. Kidney involvement may cause foamy urine or extra swelling.

Symptoms also differ by stage. Early on, a person may have only mild breathlessness or a reduced tolerance for blood pressure medicines they previously took without trouble. In later stages, fluid retention, fainting, and profound weakness may dominate. Because the pattern varies so much, no single symptom confirms the diagnosis; it is the combination of heart failure signs with these other features that usually prompts doctors to test for amyloid.

Cardiac amyloidosis causes and risk factors

Cardiac amyloidosis causes come down to which protein is misfolding. Understanding the type matters because treatment is different for each.

• Light-chain (AL) amyloidosis. This form is caused by a disorder of plasma cells, a type of white blood cell in the bone marrow. Abnormal plasma cells produce excess pieces of antibody called light chains, which misfold and deposit in tissues. AL amyloidosis is related to, and sometimes occurs with, multiple myeloma, a blood cancer of plasma cells. It can progress quickly and often affects the heart together with the kidneys.
• Hereditary transthyretin (ATTRv) amyloidosis. Transthyretin is a protein made mainly by the liver that carries thyroid hormone and vitamin A. Inherited changes (mutations) in the transthyretin gene make the protein unstable so it misfolds. This type runs in families and can affect the nerves, the heart, or both, depending on the specific gene change.
• Wild-type transthyretin (ATTRwt) amyloidosis. Here the transthyretin gene is normal, but the protein still becomes unstable with age. This form is strongly linked to aging and is thought to be underdiagnosed in older adults with heart failure and thick heart walls. It was previously called senile systemic amyloidosis.
• Other rarer types. Amyloid from long-term inflammation (AA amyloidosis) usually spares the heart, and some very rare hereditary forms involve other proteins.

Risk factors depend on the type. Older age is the main risk factor for wild-type ATTR, and it is diagnosed more often in men. A family history of amyloidosis, unexplained neuropathy, or early heart failure raises the possibility of hereditary ATTR; certain gene variants are more common in people of particular ancestries, including some of African or Afro-Caribbean descent, as well as in families from parts of Portugal, Sweden, and Japan. A history of a plasma cell disorder, such as multiple myeloma or a condition called MGUS (monoclonal gammopathy of undetermined significance, in which abnormal proteins are found in the blood without cancer), increases the chance of AL amyloidosis. Bilateral carpal tunnel syndrome, lumbar spinal stenosis, and a history of biceps tendon rupture in an older adult are recognized warning signs that amyloid may be present. Cardiac amyloidosis is not caused by lifestyle choices, diet, or infection, and it is not contagious.

Cardiac amyloidosis diagnosis

Cardiac amyloidosis diagnosis has two goals: confirming that amyloid is present in the heart, and identifying which type of protein is responsible. Doctors usually start with a detailed medical history, a physical examination, and standard heart tests, then move to more specialized tests if the picture is suspicious.

• Electrocardiogram (ECG). A recording of the heart’s electrical activity. In amyloidosis the electrical signals may appear unusually small despite thick heart walls, a mismatch that can be a clue. It also detects rhythm problems.
• Echocardiogram. An ultrasound scan of the heart. It often shows thickened walls, a stiff heart that fills poorly, enlarged upper chambers, and a characteristic pattern of reduced movement in the heart muscle. Echocardiography alone cannot prove the diagnosis, but it frequently raises suspicion.
• Cardiac MRI. A magnetic resonance scan that provides detailed pictures of the heart muscle. After a contrast dye is given, amyloid deposits tend to show a distinctive pattern that supports the diagnosis.
• Blood and urine tests. These include markers of heart strain and damage, kidney function, and, crucially, tests that look for abnormal light chains or antibody proteins (serum free light chains, serum and urine protein electrophoresis with immunofixation). These help doctors decide whether AL amyloidosis is likely.
• Bone scintigraphy (nuclear scan). A scan using a small amount of a radioactive tracer that binds strongly to transthyretin amyloid in the heart. When this scan is clearly positive and blood and urine tests show no abnormal light chains, doctors can often diagnose ATTR cardiac amyloidosis without a heart biopsy.
• Biopsy. A small tissue sample, taken from the heart itself, from abdominal fat, bone marrow, or another affected organ, is examined under a microscope with special stains that reveal amyloid. Further laboratory analysis identifies the exact protein type. A biopsy is usually required when AL amyloidosis is suspected or when other tests are inconclusive.
• Genetic testing. If ATTR is confirmed, a blood test for transthyretin gene mutations tells doctors whether the disease is hereditary or wild-type, which has implications for family members.

Because symptoms overlap with other causes of heart failure and thick heart walls, such as high blood pressure or hypertrophic cardiomyopathy, diagnosis can be delayed. Doctors may consider testing when heart failure is accompanied by neuropathy, carpal tunnel syndrome, low blood pressure, intolerance of usual heart medicines, or a family history of amyloidosis.

Cardiac amyloidosis treatment options

Cardiac amyloidosis treatment options fall into two groups: treatments aimed at the underlying amyloid process, and treatments that manage the effects on the heart. The specific plan depends heavily on the type of amyloidosis, how advanced it is, which other organs are involved, and the person’s overall health.

Treating the underlying disease

• For AL amyloidosis, treatment targets the abnormal plasma cells and is usually directed by a hematologist. Chemotherapy and related drugs, including antibody-based medicines, are used to stop production of the harmful light chains. In selected people who are fit enough, high-dose chemotherapy followed by a stem cell transplant using the person’s own cells may be considered. The heart’s condition strongly influences which treatments are safe.
• For ATTR amyloidosis, medicines have been developed that either stabilize the transthyretin protein so it is less likely to misfold, or reduce the liver’s production of transthyretin (gene-silencing therapies, given by injection). These aim to slow progression rather than reverse existing deposits. Availability and eligibility vary by country and individual circumstances, and your doctor will discuss what is appropriate.
• Liver transplant was historically used for some hereditary ATTR cases because the liver makes the abnormal protein, but its role has become more limited as medicines have improved.

Managing the heart

• Diuretics (water tablets) are a mainstay for relieving fluid buildup and breathlessness. Doses often need careful adjustment because the stiff heart is sensitive to both too much and too little fluid. Limiting salt and, if advised, fluid intake supports this.
• Caution with standard heart-failure medicines. Some drugs commonly used for other forms of heart failure, such as certain blood pressure medicines and digoxin, may be poorly tolerated or potentially harmful in amyloidosis. Doctors therefore tailor medication carefully.
• Rhythm management. Atrial fibrillation (an irregular, often fast heart rhythm) is common and usually treated with blood-thinning medicines to reduce stroke risk, along with rhythm or rate control. A pacemaker may be needed if the heart’s electrical system becomes too slow. The role of implantable defibrillators is decided case by case.
• Heart transplant may be an option for a small number of carefully selected people, sometimes combined with treatment of the underlying disease.

Supportive care and rehabilitation

Cardiac rehabilitation programs, supervised gentle exercise, nutritional support, and management of low blood pressure, neuropathy, and digestive symptoms all contribute to quality of life. Some people benefit from compression stockings or medicines to prevent blood pressure drops when standing. Palliative and supportive care teams, which focus on symptom relief and quality of life at any stage, can be involved alongside active treatment.

Living with cardiac amyloidosis and outlook

The outlook for cardiac amyloidosis varies widely and depends mainly on the type, how much the heart has been affected at the time of diagnosis, and how well the underlying disease responds to treatment. In general, AL amyloidosis with significant heart involvement has historically been the most serious form, although outcomes have improved with earlier diagnosis and newer therapies. ATTR amyloidosis usually progresses more slowly, and disease-modifying medicines have changed expectations for many people. It is not possible to predict any individual’s course, and doctors typically use staging systems based on blood tests to give a clearer picture over time.

Living well with the condition often involves regular follow-up with a cardiology team and, for AL disease, a hematology team; daily weight checks to spot fluid buildup early; taking medicines exactly as prescribed; attention to salt intake; staying as active as symptoms allow; and reporting new symptoms promptly. Vaccinations recommended by your doctor help reduce the risk of infections that can strain the heart. People with hereditary ATTR may be offered genetic counseling so relatives can decide whether to be tested. Emotional support, whether from family, counseling, or patient organizations, is an important part of coping with a rare and chronic illness.

Frequently asked questions

What is cardiac amyloidosis in simple terms?

In simple terms, cardiac amyloidosis is a disease in which misfolded proteins build up in the heart wall, making it thick and stiff. Because the stiff heart cannot fill or pump normally, symptoms of heart failure and rhythm problems develop. It is one form of a wider group of conditions called amyloidosis, in which the same protein deposits can affect other organs.

What are the earliest cardiac amyloidosis symptoms?

Early symptoms are often subtle and may include mild breathlessness with exertion, tiredness, and slight ankle swelling. Clues outside the heart, such as carpal tunnel syndrome in both wrists, numbness in the feet, or unexplained low blood pressure, may appear years before heart symptoms. Because these are common complaints with many causes, they do not mean a person has amyloidosis, but they are worth mentioning to a doctor.

What are the main cardiac amyloidosis causes?

The main causes are light-chain (AL) amyloidosis, in which abnormal bone marrow plasma cells produce misfolding antibody fragments, and transthyretin (ATTR) amyloidosis, in which a liver-made protein becomes unstable either because of an inherited gene change or simply with aging. The condition is not caused by diet, lifestyle, or infection.

How is cardiac amyloidosis diagnosis confirmed?

Doctors combine clinical suspicion with tests such as an ECG, echocardiogram, cardiac MRI, and blood and urine tests for abnormal proteins. A specialized nuclear bone scan can confirm ATTR amyloidosis in many cases without a biopsy, provided light-chain tests are normal. In other situations, a tissue biopsy is needed to prove amyloid is present and to identify the protein type, which guides treatment.

What are the cardiac amyloidosis treatment options for older adults?

Many older adults have wild-type ATTR amyloidosis. Treatment usually includes diuretics to control fluid, careful management of heart rhythm problems, and, when appropriate, medicines that stabilize transthyretin or reduce its production to slow disease progression. Treatment choices depend on overall health and other conditions, and are decided individually with the care team.

Is cardiac amyloidosis hereditary?

Only some forms are. Hereditary ATTR amyloidosis is passed down through families by a change in the transthyretin gene, and each child of an affected parent has a chance of inheriting it. Wild-type ATTR and AL amyloidosis are not inherited. Genetic testing and counseling are typically offered when a hereditary form is diagnosed.

Can cardiac amyloidosis be cured?

At present there is no treatment that reliably removes existing amyloid from the heart. For AL amyloidosis, treatments can often stop production of the harmful protein and may lead to long-lasting remission. For ATTR, medicines aim to slow or halt progression. Many people live for years with treatment and good symptom management, but outcomes vary and your doctor can discuss what is realistic for your situation.

When to see a doctor

Anyone with ongoing shortness of breath, unexplained swelling of the legs, or reduced ability to exercise should be evaluated by a doctor, particularly if these occur together with numbness or tingling in the hands or feet, carpal tunnel syndrome in both wrists, unexplained weight loss, or a family history of amyloidosis or early heart failure. A person already diagnosed with cardiac amyloidosis should keep scheduled follow-up appointments and report new or worsening symptoms promptly. Seek urgent or emergency medical care if you experience any of the following:

• Severe or rapidly worsening shortness of breath, or breathlessness that wakes you from sleep
• Fainting or near-fainting, especially if repeated
• Chest pain or pressure that does not go away
• A very fast, very slow, or irregular heartbeat with dizziness or weakness
• Sudden weakness or numbness of the face, arm, or leg, trouble speaking, or vision loss, which may signal a stroke
• Rapid weight gain of several pounds over a few days with increasing swelling
• Confusion, extreme drowsiness, or inability to stay awake
• Very low urine output or signs of dehydration after vomiting or diarrhea while taking diuretics

These signs may indicate a serious change in heart function or rhythm that needs prompt assessment.